Due to the recent improvements in B0 gradient and rf coils, 1H MR spectra have been recorded in the human brain with excellent water suppression. Using TE (Time for a spin Echo) as short as 15 ms, several cerebral metabolites have been identified; see Hanstock, C C, Rothman, D L, Prichard, J W, Jue, T, Shulman, R G, (1988), “Spatially Localized NMR spectra of metabolites in the human brain”, PNAS (USA), 85:18215; Braun H, Frahm J, Gyngell M L, Merboldt K D, Hanicke W and Suter R, (1989), “Cerebral metabolism in man after acute stroke: New observation using localized proton NMR Spectroscopy”, Magn Reson Med, 9: 126–131; Kuzniecky R, Hetherington H, Pan J, et al., (1997), “Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy”, Neurology, 48:1018–1024; Barberi E A, Gai J S, Rutt B K and Menon R S, (2000), “A transmit-only/receive only (TORO) system for high field MRI/MRS applications”, Magn Reson Med, 43:284–289. During the past decade, alterations in several metabolites, namely N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline (Ch), creatine (Cr), myo-inositol (ml) and γ-aminobutyrate (GABA) have been reported in different pathologies; see Kreis R, Ross B D, Farrow N and Ackerman Z, (1992), “Metabolic disorders of the brain in chronic hepatic encephalopathy detected with 1H MR Spectroscopy”, Radiology, 182: 9–27; Chang L, Ernst T, Yee M L, Walot I and Singer E., (1999), “Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex”, Neurology, 52:100–108; Thomas M A, Huda A, Guze B et al., (1998), Cerebral 1H MR “Spectroscopy and Neuropsychological status of patients with Hepatic Encephalopathy”, Am. J. Roentgenology, 171: 1123–1130; Thomas M A, Ke Y, Levitt J, et al., (1998), “Preliminary Study of Frontal Lobe 1H MR Spectroscopy in Childhood-Onset Schizophrenia”, J Magn Reson Ima, 8:841–846; Narayana P A, Doyle T J, Lai D and Wolinsky J S, (1998), “Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in Multiple Scelerosis”, Ann Neurol, 43:56–71; Haseler L J, Sibbitt W L, Mojtahedzadeh H N, et al., (1998), “Proton MR spectroscopic measurement of neurometabolites in HE during oral Lactulose Therapy”, AJNR, 19:1681–1686. Absolute quantitation of cerebral metabolites has also been reported for only a few metabolites with a limited success in vivo; see Michelis T, Merboldt K D, Bruhn H, Hanicke W, and Frahm J, (1993), “Absolute concentrations of metabolites in the adult human brain in vivo: Quantification of localized proton MR Spectra”, Radiology, 187: 219–227; Ernst T, Kreis R and Ross B D, (1993), “Absolute Quantitation of water and metabolites in the human brain. I. Compartments and water”, J Magn Reson, B 102: 1–8; Rothman, D I, Petroff, OAC, Behar, K L and Mattson, R H, (1993), “Localized 1H NMR measurements of γ-aminobutyric acid in human brain in vivo”, Proc Natl Acad Sci USA, 90: 5662–5666.
Due to severe overlap of these metabolites, an unambiguous assignment of J-coupled metabolite multiplets is severely hindered at 1.5T field strength.
One-dimensional (1D) MR spectral editing techniques, used to unravel the overlapping resonance, rely on J-coupled proton metabolites, which have well separated multiplets. However, techniques based on subtraction methodology are very sensitive to motion artifacts leading to subtraction errors. An additional drawback is that only one metabolite can be identified at a time. Successful attempts in editing GABA and glutamate using whole body MRI/MRS scanners have been presented by other researchers; see Rothman et al., supra; Behar K L, Rothman D L, Spencer D D, Petroff O A C, (1994), “Analysis of macromolecule resonance in 1H NMR spectra of human brain”, Magn Reson Med, 32:294–302; Pan J W, Mason G F, Vaughan J T,Chu W J, Zhang Y and Hetherington, (1997), “13C Editing of glutamate in human brain using J-refocused coherence transfer spectroscopy”, Magn Reson Med, 37:355–35. Single-shot based multiple-quantum filtered MR spectroscopic sequences have also been implemented on whole body scanners, but a severe loss of signal associated with various coherence transfer pathways made it less attractive to human applications; see Keltner J R, Wald L L, Frederick B d B, Renshaw P F, (1997), “In vivo detection of GABA in human brain using a localized double-quantum filter technique”, Magn Reson Med, 37:366–371; Thomas M A, Hetherington H P, Meyerhoff D J and Twieg D, (1991), “Localized Double Quantum filtered NMR Spectroscopy”, J Magn Reson, B93: 485–496; Wilman A, Allen P, (1993), “In vivo NMR detection strategies for gamma-aminobutyric acid, utilizing proton spectroscopy and coherence-pathway filtering with gradients”, J Magn Reson, B101: 165–171.
A localized version of a two-dimensional (2D) J-resolved MR spectroscopic (JPRESS) sequence, using the Point Resolved Spectroscopic Sequence (PRESS} sequence for volume localization, was proposed recently; see Ryner L N, Sorenson J A and Thomas M A, (1995), “3D localized 2D NMR Spectroscopy on an MRI scanner”, J.Magn.Reson, series B,107: 126–137; Ryner L N, Sorenson J A and Thomas M A, (1995), “Localized 2D J-Resolved 1H MR Spectroscopy: Strong coupling effects in vitro and in vivo”, Magn.Reson. Ima., 13: 853–869; Thomas M A, Ryner L N, Mehta M, Turski P and Sorenson J A, (1996), J. Magnetic Resonance Imaging, 6: 453–459. Even though the JPRESS sequence retains 100% of the magnetization from a localized volume of interest (VOI), the strong coupling effect inherent at 1.5 T field strength resulted in a complex 2D cross peak pattern for NAA, glutamate/glutamine, GABA and other cerebral metabolites; see Ryner et al., (“Localized 2D J-Resolved . . . ”), supra. Moreover, some of the 2D cross peaks were heavily T2-weighted during the long incremental delays necessitated by the second dimension of the JPRESS spectrum. An oversampled 2D J-resolved sequence has also been proposed recently; see Hurd R E, Gurr D and Sailasuta N, (1998), Proton Spectroscopy without water suppression: the oversampled J-resolved experiment, Magn Reson Med, 40:343–34. In addition, homonuclear decoupled in vivo 1H MR spectra using constant time chemical shift encoding were presented by Leibfritz and co-workers; see Dreher W and Leibfritz D, (1999), “Detection of Homonuclear Decoupled in vivo proton NMR spectra using constant time chemical shift encoding: CT-PRESS”, Magn Reson Ima, 17:141–150.
Compared to the localized 2D JPRESS spectra, a better dispersion of J-cross peaks is conceivable in a COSY spectrum, albeit a larger spectral window needs to be sampled during the evolution period; see Ernst R R, Bodenhausen G and Wokaun A, (1987), “Principles of NMR Spectroscopy in one and two dimensions”, Oxford Publications, Oxford. Different versions of the localized COSY sequence have been implemented by other researchers; see McKinnon G C and Bosiger P, (1988), “Localized Double Quantum filter and correlation spectroscopy experiments”, Magn Reson Med, 6:334–343; Haase A, Schuff N, Norris D, Leibfritz D, (1987), Proc SMRM, 1051; Cohen Y, Chang L H, Litt L, James T L, (1989), “Spatially Localized COSY spectra from a surface coil using phase-encoding magnetic field gradients”, J Magn Reson, 85:203–208; Blackband S J, McGovern K A, McLennan I J, (1988), “Spatially localized two-dimensional spectroscopy. SLO-COSY and SLO-NOESY”, J Magn Reson, 79: 184–189; Behar K L, Ogino T., (1991), “Assignment of Resonance in the 1H Spectrum of rat brain by Two-dimensional shift correlated and J-resolved NMR spectroscopy”, Magn Reson Med, 17:285–303; de Graaf R A, Kranenburg A V and Nicolay K., (1999), “Off-resonance Metabolite Magnetization transfer measurements on rat brain in situ”, Magn Reson Med, 41:1136–1144; Kreis R and Boesch C., (1996), “Spatially Localized, one- and two-dimensional NMR Spectroscopy and in vivo application to human muscle”, J Magn Reson, B113:103–118. McKinnon and Bosiger proposed a conventional COSY sequence with hard rf pulses (90°-t1-90°) followed by three volume selective 180° rf pulses; see McKinnon and Bosiger, supra. Haase and co-workers implemented a COSY combined with an outer volume suppressing sequence, namely the Localization of Unaffected Spins sequence, LOCUS; see Haase et al., supra. Many of these previous attempts to develop localized 2D COSY spectra yielded only phantom results or rat brain spectra using a surface coil without a built-in localization sequence; see McKinnon and Bosiger, supra; Haase et al., supra; Cohen et al., supra; Blackband et al., supra; Behar and Ogino, supra.
A new gradient enhanced COSY in combination with Volume Localized Spectroscopy (VOSY) used the Stimulated Echo Acquisition Mode (STEAM) sequence for volume localization; see Brereton I M, Galloway G J, Rose S E and Doddrell D M, (1994), “Localized two-dimensional shift correlated and J-resolved NMR spectroscopy”, Magn Reson Med, 17:285–303. Moreover, a human brain 2D COSY spectrum using a 2T MRI scanner was recorded in a gross occipital volume of 5×6×8 cm3, which required a total sampling duration of 1 hour and 42 minutes; see Brereton and Galloway et al., supra.
Non-localized versions of COSY spectra have also been recorded in rat brain and rabbit kidney by other researchers using high field NMR spectrometers; see Peres M, Fedeli O, Barrere B, et al., (1992), “In vivo identification and monitoring of changes in rat brain glucose by two-dimensional shift-correlated 1H NMR Spectroscopy”, Magn Reson Med, 27:356–361; Berkowitz B A, Wolff S D and Balaban R S, (1988), “Detection of metabolites in vivo using 2D proton homonuclear correlated spectroscopy”, J Magn Reson, 79:547–553.
Two major problems yet to be resolved in the localized 2D MR spectroscopy are: 1) minimizing the rf pulses used for both localization and coherence transfer taking into consideration that some of the brain metabolites have short repetition time, T2, and 2) recording the localized 2D spectra of human organs in a reasonable time duration. The goals of this work are two-fold: 1) to implement a new version of a localized 2D COSY sequence (L-COSY) and its 1D analog on a 1.5 T whole body MRI/MRS scanner with a minimal number of rf pulses for volume localization and coherence transfer, and 2) to record L-COSY spectra in the frontal and occipital gray/white matter of healthy human brains.